•Diabetic neuropathy is a common complication of both Type 1 diabetes and Type 2 diabetes. Neuropathy plays a major role in the development of foot ulcers, which cause an enormous burden on quality of life for the patient (especially if amputation becomes necessary) and is also responsible for a very large health and social services expenditure.

•Optimal control of all metabolic factors and regular organised surveillance of all people with diabetes is essential to reduce the risk of both development and progression of diabetic neuropathy and therefore reduce the risk of disability for the patient.
•Motor, sensory, and autonomic fibres may all be affected by diabetic neuropathy.

.Risk factors
•Aged over 40 years
•History of periods of poor glycaemic control
•Prevalence increases with increased duration of diabetes
•People with signs of neuropathy are likely to also have evidence of diabetic nephropathy and diabetic retinopathy
•Ischaemic heart disease

.Peripheral sensorimotor (Chronic peripheral neuropathy)
•Sensory nerves are affected more than motor.
•Touch, pain and temperature sensation and proprioception in lower limbs in a glove and stocking distribution.
•Loss of ankle jerks and later knee jerks.
•Hands are only affected in severe longstanding neuropathy.
•Equal prevalence in Types 1 and 2.

.Acute diffuse painful (acute peripheral neuritis)
•Often abrupt onset and not related to duration of diabetes.
•Can resolve completely.
•Burning foot pain, often worse at night.
•Associated with poor glycaemic control but sometimes initially follows establishing good glycaemic control.
•Examination may be normal apart from hyperaesthesia.

.Autonomic neuropathy
•Risk factors include hypertension and dyslipidaemia. Is more common in females.
•May present with:

■Impotence, retrograde ejaculation, urinary hesitancy, overflow incontinence
■At least 25% male diabetics have problem with sexual function
■There is often no association with glycaemic control, duration or severity of diabetes
■Risk factors for erectile dysfunction include increasing age, alcohol, initial glycaemic control, intermittent claudication and retinopathy

nausea and vomiting, abdominal distension, dysphagia, diarrhoea

◦Gustatory sweating, anhidrosis

◦Dizziness due to postural hypotension

•Tends to be associated with peripheral neuropathy
•People with both Type 1 and 2 are affected
•High mortality rate (50% within 3 years) mainly due to renal failure but often no obvious cause
•Tight glycaemic control reduces the risk

•External pressure or entrapment, e.g. carpal tunnel syndrome.
•Isolated neuropathies of either cranial or peripheral nerves. Mononeuropathies of cranial nerves III, IV, and VI, intercostal nerves, and femoral nerves are common.
•Occasionally more than one nerve is involved (mononeuritis multiplex).

.Proximal motor (diabetic amyotrophy)
•Main motor manifestation.
•Severe pain and paraesthesiae in upper legs, with weakness and muscle wasting of thigh and pelvic girdle muscles.
•May be asymmetrical and there may be extensor plantars.
•Mainly affects middle-aged and elderly patients.
•Usually associated with period of very poor glycaemic control, sometimes with dramatic weight loss.
•Pain and weakness gradually reduce once good glycaemic control has returned.

Early features of neuropathy often go unrecognised by the patient, further emphasising the importance of routine surveillance..

.Differential diagnosis
•Other possible causes of neuropathy include:
•Toxins, e.g. alcohol, occupational, vitamin B6, medications (e.g. amiodarone)
•Pernicious anaemia
•Malignancies, amyloidosis
•Collagen vascular disease, neurosarcoidosis
•Tabes dorsalis, AIDs
•Spinal cord disease, cauda equina syndrome

•Full assessment of diabetes and blood pressure control. Assessment of other possible causes, e.g. thyroid function tests, B12.
•May require nerve conduction studies and EMG.

•Regular surveillance for signs of neuropathy to allow early intervention.
•Tight glycaemic control.
•Prevention of foot trauma.

.Management of painful neuropathy
•May require a great deal of support for the depressing and disabling nature of the condition

•Consider initially:
◦Bed foot cradles for night-time problems
◦Simple analgesia taken in advance of diurnal symptoms
◦Contact dressings

•Drug treatments:
◦Oral tricyclic antidepressants and traditional anticonvulsants are better for short term pain relief than newer generation anticonvulsants.1
◦Evidence of the long term effects of oral antidepressants and anticonvulsants is still lacking.1
◦Therefore consider therapeutic trials of:1

■Tricyclic antidepressants (TCAs) and topical capsaicin should be used as first line therapy in painful diabetic neuropathy.1
■Traditional anticonvulsants (sodium valproate, carbamazepine) should be considered if insufficient symptom control.
■Newer anticonvulsants (gabapentin, pregabalin) should next be considered if necessary.
■Duloxetine and then opioids may be required if symptom control is still inadequate.1

.Management of autonomic neuropathy
The only treatment for autonomic neuropathy is to treat symptoms. In all patients, optimise diabetic control..

•Erectile dysfunction

◦Investigation using radiological or radioisotope methods may help in diagnosis
◦Investigation of cardiovascular autonomic neuropathy may help diagnosis
◦Metoclopramide and domperidone are worth a trial

•Diabetic nocturnal diarrhoea
◦Investigation must exclude other causes of intestinal upset
◦May be helped by high doses of codeine, loperamide or diphenoxylate, or by erythromycin or tetracycline

•Gustatory sweating
◦Explanation and counselling are often required
◦Topical or oral anticholinergic agents (eg. poldine methylsulphate) may be effective

•Postural hypotension
◦May respond to fludrocortisone

•Autonomic neuropathy is associated with high mortality rate (50% within 3 years) mainly due to renal failure or cardiovascular effects but often no obvious cause.
•Diabetics are 15-70 times more likely to undergo lower limb amputation than non-diabetics.

•Tight glycaemic control has been clearly shown to reduce the risk of neuropathy.
•Smoking avoidance or cessation.

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